Macugen® (Pegaptanib Sodium ) is indicated for the treatment of patients with:

• neovascular (wet) age-related macular degeneration

The recommended dosage regimen of pegaptanib sodium is 0.3 mg to be administered by intravitreal injection once every six weeks.

Lucentis® (ranibizumab) is indicated for the treatment of patients with:

• neovascular (wet) age-related macular degeneration

The recommended dosage regimen of ranibizumab is 0.5 mg (0.05 mL) to be administered by intravitreal injection once a month (approximately 28 days).

Although less effective, treatment may be reduced to one injection every three months after the first four injections if monthly injections are not feasible. Compared to continued monthly dosing, dosing every 3 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average, over the following 9 months. Patients should be treated regularly.

• macular edema following retinal vein occlusion (RVO)(central & branch)

The recommended dosage regimen of ranibizumab is 0.5 mg (0.05 mL) to be administered by intravitreal injection once a month (approximately 28 days).

In the RVO clinical studies, patients received monthly injections for six months. In spite of being guided by optical coherence tomography and visual acuity re-treatment criteria, patients who were then not treated at month 6 experienced on average, a loss of visual acuity at month 7, whereas patients who were treated at month 6 did not. Patients should be treated monthly.

Eylea™ (afibercept) is indicated for the treatment of patients with:

•  neovascular (wet) age-related macular degeneration

The recommended dose of afibercept is 2 mg (0.05 mL) to be administered by intravitreal injection every 4 weeks (monthly) for the first 3 months, followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months).

Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (monthly), additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks.

The use of afibercept, ranibizumab, or pegaptanib sodium for any other indication is considered experimental/investigational, and therefore, not covered. A participating, preferred, or network provider can bill the member for the non-covered service.

NOTE:

Coverage for ranibizumab is determined according to individual or group customer benefits. Ranibizumab is not reimbursable under the prescription drug benefit.

Description

Pegaptanib is an aptamer, a pegylated modified oligonucleotide that is a selective vascular endothelial growth factor (VEGF) antagonist, a type of signal-transduction inhibitor (STI) and angiogenesis inhibitor. The drug works by targeting a very specific VEGF isoform involved in the disease process of AMD, known as VEGF-165.

Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). VEGF-A has been shown to cause neovascularization and leakage in models of ocular angiogenesis and is thought to contribute to the progression of the neovascular form of age-related macular degeneration (AMD). The binding of ranibizumab to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.

Afibercept is a recombinant fusion protein. It binds vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF), and thereby inhibits the binding and activation of these receptors.

NOTE:

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Under the Federal Employee Program, all services that utilize FDA-approved drugs, devices, or biological products are eligible when intended for the treatment of a serious or live-threatening condition and when medically necessary and appropriate for the patient's condition.

Lucentis® (ranibizumab injection)[package insert]. Genentech, Inc., South San Francisco, CA. 06/2010.

Lu M, Adamis AP. Molecular biology of choroidal neovascularization. Ophthalmol Clinics of NA. 2006;19:323-334.

Shams N. Role of vascular endothelial growth factor in ocular angiogenesis. Ophthalmol Clinics of NA. 2006;19:335-344.

Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-1444.

Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: phase III clinical trial results; Ophthalmol Clinics of NA. 2006;19:361-372.

Mitka M. Study aims to clarify efficacy, safety of eye drug treatments. JAMA. 2007;297:1538-1539.

Mohamed Q, Gillies M, Wong TY, et al. Management of Diabetic Retinopathy. JAMA. 2007;298:902-916.

Aiello LP. Targeting intraocular neovascularization and edema - one drop at a time. N Engl J Med. 2008;359:967-969.

Jager RD, Mieler WR, Miller JW. Age-related macular degeneration. N Engl J Med. 2008;358:2606-2617.

Regillo CD, Brown DM, Abraham P, Yeu H, et al. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: Pier study year 1. Am J Ophthalmol. 2008;145:239-248.

Antoszyk AN, Tuomi L, Chung CY, et al. Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration (FOCUS): year 2 results. Am J of Ophthalmol. 2008;145:862-874.

Spaide RF, Chang LK, Klancnik JM, et al. Prospective study of intravitreal ranibizumab as a treatment for decreased visual acuity secondary to central retinal vein occlusion. Am J Ophthalmol. 2009;147:298-306.

Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: Six-month primary end point results of a phase III study. Ophthalmology. 2010;117(6):1124-1133.

Massin P, Bandello F, Garweg JG, et al. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE study) a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care. 2010;33:2399-2405.

Kinge B, Stordahl PB, Forsaa V, et al. Efficacy of ranibizumab in patients with macular edema secondary to central retinal vein occlusion: results from the sham-controlled ROCC study. Am J Ophthalmol. 2010;150(3):310-314.

Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal vein occlusion: Six-month primary end point results of a phase III study. Ophthalmology. 2010;117:1102-1112.

Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2012. URL: http://cp.gsm.com. Updated November 2011.

Dhoot DS, Kaiser PK. Ranibizumab for age-related macular degeneration. Expert Opin Biol Ther. 2012 Feb 6.

Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for Diabetic Macular Edema: Results from 2 Phase III Randomized Trials: RISE and RIDE. Ophthalmology. 2012 Feb 11.

Ohr M, Kaiser PK. Intravitreal Afibercept injection for neovascular (wet) age-related macular degeneration. Expert Opin Pharmacother. 2012 Feb 3.

Papadopoulos N, Martin J, Ruan Q, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012 Feb 3.

Stewart MW, Rosenfeld PJ, Penha FM, et al. Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and Afibercept (vascular endothelial growth factor trap-eye). Retina. 2011 Dec 18.

Eylea™ (afibercept injection)[package insert]. Regeneron Pharmaceuticals, Inc., Tarrytown, NY. 11/2011.

Macugen® (pegaptanib sodium injection)[package insert]. Pfizer, Inc., New York, NY. 2006.